In the past 5 year, the MSKCC investigators have performed clinical trials involving a variety of signal transduction agents as well as novel agents of unusual mechanism. The center has extensive experience in the conduct of Phase I studies related to small molecules, monoclonal antibodies and vaccines. This research proposes to develop new information relevant to the treatment of cancer by conducting Phase I studies of new anticancer drugs and pharmacologic modulatory regimens which attempt to enhance the therapeutic efficacy of new drugs. Concurrent with the clinical studies, the research will evaluate the distribution and metabolism of the study drugs and examine their biological effects at the clinical biochemical and molecular level. The Specific Aims will be to perform Phase I clinical trials with agents from the following classes: 1) Modulators of epigenetic regulation of gene expression (putative differentiation therapy) such as retinoids, histone deacetylase inhibitors and demethylating agents; 2) Signal Transduction Targets such as protein kinase C, AKT, HER2 and cell cycle dependent kinases; 3) Phase I Testing of Tumor (Histology Specific) Therapies such as agents appropriate for a single tumor type like prostate cancer; and 4) Immunologic Therapy. The planned clinical trials are to be awarded by the CTEP staff in response to LOI's. We hope to take advantage of the laboratory insights provided by laboratory and clinical investigators at the MSKCC to provide new hypotheses for Phase I clinical testing. Correlative sciences including pharmacokinetics, gene expression, protein expression, functional imaging and assessment of endpoints in biopsy material are expected to be a major part of the studies to be done. [unreadable] [unreadable] [unreadable]